1TA6: Crystal Structure Of Thrombin In Complex With Compound 14b

Citation:
Abstract
As part of an ongoing effort to prepare therapeutically useful orally active thrombin inhibitors, we have synthesized a series of compounds that utilize nonbasic groups in the P1 position. The work is based on our previously reported lead structure, compound 1, which was discovered via a resin-based approach to varying P1. By minimizing the size and lipophilicity of the P3 group and by incorporating hydrogen-bonding groups on the N-terminus or on the 2-position of the P1 aromatic ring, we have prepared a number of derivatives in this series that exhibit subnanomolar enzyme potency combined with good in vivo antithrombotic and bioavailability profiles. The oxyacetic amide compound 14b exhibited the best overall profile of in vitro and in vivo activity, and crystallographic studies indicate a unique mode of binding in the thrombin active site.
PDB ID: 1TA6Download
MMDB ID: 27946
PDB Deposition Date: 2004/5/19
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 1TA6: dimeric; determined by author and by software (PISA)
Molecular Components in 1TA6
Label Count Molecule
Proteins (2 molecules)
1
Thrombin(Gene symbol: F2)
Molecule annotation
1
Hirudin
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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